1-Isopropylhydrazine hydrochloride → 9-Bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,10b-diaza-benzo[e]azulene

HRID 1629100Notes

Reaction equation

HRID 1629100 reaction equation
C[N:2](C)[CH:3]=[N:4][C:5]([C:7]1[CH:8]=[C:9]2[N:15]([N:16]=1)[C:14]1[CH:17]=[C:18]([Br:21])[CH:19]=[CH:20][C:13]=1[O:12][CH2:11][CH2:10]2)=O.Cl.[CH:24]([NH:27]N)([CH3:26])[CH3:25]>C(O)(=O)C>[Br:21][C:18]1[CH:19]=[CH:20][C:13]2[O:12][CH2:11][CH2:10][C:9]3[N:15]([N:16]=[C:7]([C:5]4[N:27]([CH:24]([CH3:26])[CH3:25])[N:2]=[CH:3][N:4]=4)[CH:8]=3)[C:14]=2[CH:17]=1

Participants

4

Reactant 2

HCID 855731-Isopropylhydrazine hydrochlorideHCID 582044179-Bromo-4,5-dihydro-6-oxa-1,10b-diaza-benzo[e]azulene-2-carboxylic acid 1-dimethylaminomethylideneamide

Product 1

HCID 582047309-Bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,10b-diaza-benzo[e]azuleneYield 76%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 9-bromo-4,5-dihydro-6-oxa-1,10b-diaza-benzo[e]azulene-2-carboxylic acid 1-dimethylaminomethylideneamide (1.27 g, 3.5 mmol), isopropylhydrazine hydrochloride (0.48 g, 4.37 mmol) and glacial acetic acid (6 mL) was heated at 110° C. for 6.5 h, then cooled and concentrated in vacuo. The resultant residue was dissolved in aqueous sodium bicarbonate and DCM and the phases were separated. The aqueous phase was extracted several times with DCM, the combined organic extracts dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 30 to 70% ethyl acetate in cyclohexane) to give 9-Bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,10b-diaza-benzo[e]azulene (0.99 g, 76%). LCMS: RT=5.07 min, M+H+=374/376. 1H NMR δ (ppm)(CDCl3): 8.07 (1 H, d, J=2.41 Hz), 7.96 (1 H, s), 7.39 (1 H, dd, J=8.63, 2.43 Hz), 7.08 (1 H, d, J=8.63 Hz), 6.91 (1 H, s), 5.73-5.65 (1 H, m), 4.53 (2 H, t, J=5.91 Hz), 3.18 (2 H, t, J=5.91 Hz), 1.60 (6 H, d, J=6.62 Hz)

Workup

  1. temperaturecooled
  2. concentrationconcentrated in vacuo
  3. dissolutionThe resultant residue was dissolved in aqueous sodium bicarbonate
  4. customDCM and the phases were separated
  5. extractionThe aqueous phase was extracted several times with DCM
  6. dry with materialthe combined organic extracts dried (MgSO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-8631d63a33f64e06a9b7a61e70b3cfcd
Source dataset
uspto-grants-2014_07
Patent number
US08785626B2

Reaction notes

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